Because the nutrients needed for tumor cell proliferation and tumor growth are supplied by blood vessels, malignant cells must again undergo angiogenesis to result in a clinically relevant secondary tumor that eventually forms macro‐metastases.[17] Importantly, studies have shown that enhanced EMT, stemness, and angiogenesis are partly associated with abnormally activated Wnt/β‐catenin pathways in cancer.[18] In this study, we identified β‐catenin and its‐mediated cancer stemness, EMT, and angiogenesis as downstream signaling of SAMD9 in ESCC progression. Here, SAMD9 is linked to esophageal squamous cell carcinoma.